Publication

Natural competence of the pathogen Acinetobacter baumannii: an elusive phenomenon

Nina Vesel
2022
EPFL thesis
Abstract

Natural competence for transformation is an important driver of horizontal DNA exchange between different organisms. This can result in accumulation of dangerous genetic features, such as antibiotic resistance genes, in a single organism. One example of an organism that frequently acquires antibiotic resistance genes is Acinetobacter baumannii, a Gram-negative opportunistic pathogen that has recently become problematic in hospital settings. Even though natural competence for transformation was demonstrated for some A. baumannii isolates, its competence regulon, the exact mechanism of DNA uptake, and the contribution of transformation to the acquisition of antibiotic resistance genes were largely unexplored at the beginning of this thesis. The aim of this thesis was therefore to better characterize optimal conditions of competence, the underlying competence regulon, and the necessary set of machinery proteins. Additionally, we aimed to identify the limiting factors that oppose transformation-mediated exchange of DNA in a small selection of strains. Here, we first addressed the general aspects of natural transformation, such as the competence window and the DNA uptake machinery. Our results showed that transformation is growth phase-dependent in A. baumannii and correlated with type IV pili (T4P) production. We demonstrated that T4P are essential for transformation and surface-associated motility but are only produced in a subfraction of the bacterial population. Furthermore, T4P production and assembly were under control of the PilSR two component system and the chemotaxis-like Pil-Chp system, respectively. These two regulatory systems were essential for competence development in A. baumannii, which is in contrast to what was observed for its close relative A. baylyi. We also investigated the reasons for non-transformability of certain A. baumannii isolates. We showed that comM interruption as well as the diversity of PilA protein sequences did not explain the strains' non-transformability. Instead, decreased expression of certain pilus genes was associated to the absence of transformability, which was also reflected in the protein level of the major component of T4P - PilA. Since the previously identified regulators could not explain the reduced transcript levels of the respective pilus genes, a transposon sequencing screen was performed to identify novel transformation-relevant genes. By comparison of transcriptional profiles of such genes between the transformable and non-transformable strains, we identified possible candidates that might explain non-transformability. Lastly, we explored whether the epigenome can influence A. baumannii's transformability. Our results showed that the source of transforming DNA has a significant effect on transformation of certain, yet not all tested strains. Specifically, for strain A118 the transformation levels were significantly decreased when non-self DNA was used as the donor DNA. Consequently, we identified a A118-specific restriction modification (RM) system that methylated specific DNA sequences in this strain and fostered the discrimination of self versus foreign DNA. Collectively, the findings of this thesis deciphered several important aspects of natural transformation in A. baumannii, which might ultimately help to better understand the spread of antibiotic resistance genes in this organism.

About this result
This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.
Related concepts (37)
Pilus
A pilus (Latin for 'hair'; : pili) is a hair-like appendage found on the surface of many bacteria and archaea. The terms pilus and fimbria (Latin for 'fringe'; plural: fimbriae) can be used interchangeably, although some researchers reserve the term pilus for the appendage required for bacterial conjugation. All conjugative pili are primarily composed of pilin – fibrous proteins, which are oligomeric. Dozens of these structures can exist on the bacterial and archaeal surface.
Natural competence
In microbiology, genetics, cell biology, and molecular biology, competence is the ability of a cell to alter its genetics by taking up extracellular ("naked") DNA from its environment in the process called transformation. Competence may be differentiated between natural competence, a genetically specified ability of bacteria which is thought to occur under natural conditions as well as in the laboratory, and induced or artificial competence, which arises when cells in laboratory cultures are treated to make them transiently permeable to DNA.
Horizontal gene transfer
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the evolution of many organisms. HGT is influencing scientific understanding of higher order evolution while more significantly shifting perspectives on bacterial evolution.
Show more
Related publications (95)

Capsular Polysaccharide Restrains Type VI Secretion in Acinetobacter baumannii

Melanie Blokesch, Loriane Bader, Mary-Claude Croisier-Coeytaux, Nicolas Olmo Flaugnatti

The type VI secretion system (T6SS) is a sophisticated, contact-dependent nanomachine involved in interbacterial competition. To function effectively, the T6SS must penetrate the membranes of both attacker and target bacteria. Structures associated with th ...
2024

Machine learning method for the classification of the state of living organisms' oscillations

Sandor Kasas, María Inés Villalba

The World Health Organization highlights the urgent need to address the global threat posed by antibiotic-resistant bacteria. Efficient and rapid detection of bacterial response to antibiotics and their virulence state is crucial for the effective treatmen ...
Frontiers Media Sa2024

Dangerous acquaintances: the interplay between type IV pili and the type VI secretion system during Vibrio cholerae's environmental lifestyle

Simon Bernhard Otto

Cholera, caused by the bacterium Vibrio cholerae, has affected humanity throughout history and still impacts millions of people every year. Apart from being a human pathogen, V. cholerae is a common member of the aquatic environment. Due to this natural re ...
EPFL2024
Show more
Related MOOCs (19)
Neuroscience Reconstructed: Cell Biology
This course will provide the fundamental knowledge in neuroscience required to understand how the brain is organised and how function at multiple scales is integrated to give rise to cognition and beh
Neuroscience Reconstructed: Cell Biology
This course will provide the fundamental knowledge in neuroscience required to understand how the brain is organised and how function at multiple scales is integrated to give rise to cognition and beh
Neuroscience Reconstructed: Genetics and Brain Development
This course will provide the fundamental knowledge in neuroscience required to understand how the brain is organised and how function at multiple scales is integrated to give rise to cognition and beh
Show more